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Determination of Interfacial Amorphicity in Functional Powders
SP Tech Res Inst Sweden, SP Chem Mat & Surfaces, Box 5607, SE-11486 Stockholm, Sweden.;KTH Royal Inst Technol, Div Surface & Corros Sci, Drottning Kristinas Vag 51, SE-10044 Stockholm, Sweden..
SP Tech Res Inst Sweden, SP Chem Mat & Surfaces, Box 5607, SE-11486 Stockholm, Sweden..
Novartis Pharma AG, GDC, Novartis Inst Biomed Res, Novartis Campus, CH-4002 Basel, Switzerland..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
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2017 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 33, no 4, 920-926 p.Article in journal (Refereed) Published
Abstract [en]

The nature of the surfaces of particles of pharmaceutical ingredients, food powders, and polymers is a determining factor for their performance in for example tableting, powder handling, or mixing. Changes on the surface structure of the material will impact the flow properties, dissolution rate, and tabletability of the 2 powder blend. For crystalline materials, surface amorphization is a phenomenon which is known to impact performance. Since it is important to measure and control the level of amorphicity, several characterization techniques are available to determine the bulk amorphous content of a processed material. The possibility of characterizing the degree of amorphicity at the surface, for example by studying the mechanical properties of the particles' surface at the nanoscale, is currently only offered by atomic force microscopy (AFM). The AFM PeakForce QNM technique has been used to measure the variation in energy dissipation (eV) at the surface of the particles which sheds light on the mechanical changes occurring as a result of amorphization or recrystallization events. Two novel approaches for the characterization of amorphicity are presented here. First, since particles are heterogeneous, we present a methodology to present the results of extensive QNM analysis of multiple particles in a coherent and easily interpreted manner, by studying cumulative distributions of dissipation data with respect to a threshold value which can be used to distinguish the crystalline and amorphous states. To exemplify the approach, which is generally applicable to any material, reference materials of purely crystalline alpha-lactose monohydrate and completely amorphous spray dried lactose particles were compared to a partially amorphized alpha-lactose monohydrate sample. Dissipation data are compared to evaluations of the lactose samples with conventional AFM and SEM showing significant topographical differences. Finally, the recrystallization of the surface amorphous regions in response to humidity was followed by studying the dissipation response of a well-defined surface region over time, which confirms both that dissipation measurement is a useful measure of surface amorphicity and that significant recrystallization occurs at the surface in response to humidity.

Place, publisher, year, edition, pages
2017. Vol. 33, no 4, 920-926 p.
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-317609DOI: 10.1021/acs.langmuir.6b03969ISI: 000393269700010OAI: oai:DiVA.org:uu-317609DiVA: diva2:1082506
Available from: 2017-03-16 Created: 2017-03-16 Last updated: 2017-11-29Bibliographically approved
In thesis
1. Process-induced disorder of pharmaceutical materials: Mechanisms and quantification of disorder
Open this publication in new window or tab >>Process-induced disorder of pharmaceutical materials: Mechanisms and quantification of disorder
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

One of the most important prerequisites in the drug development is to attain a reproducible and robust product in terms of its nature, and its chemical and physical properties. This can be challenging, since the crystalline form of drugs and excipients can be directly transformed into the amorphous one during normal pharmaceutical processing, referred to as process-induced amorphisation or process-induced disorder. The intention of this thesis was to address the mechanisms causing disorder during powder flow and milling and, in association with this, to evaluate, the ability of Raman spectroscopy and atomic force microscopy (AFM) to quantify and characterize process-induced disorder.

The amorphisation mechanisms were controlled by stress energy distribution during processing, which in turn was regulated by a series of process parameters. Compression and shearing stress caused by sliding were stress types that acted on the particles during powder flow and ball milling process. However, sliding was the most important inter-particulate contact process giving rise to amorphisation and the transformation was proposed to be caused by vitrification. The plastic stiffness and elastic stiffness of the milling-induced particles were similar to a two-state particle model, however the moisture sorption characteristics of these particles were different. Thus the milled particles could not be described solely by a two-state particle model with amorphous and crystalline domains. 

Raman spectroscopy proved to be an appropriate and effective technique in the quantification of the apparent amorphous content of milled lactose powder. The disordered content below 1% could be quantified with Raman spectroscopy. AFM was a useful approach to characterize disorder on the particle surfaces.

In summary, this thesis has provided insight into the mechanisms involved in process-induced amorphisation of pharmaceutical powders and presented new approaches for quantification and characterization of disordered content by Raman spectroscopy and atomic force microscopy.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 69 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 228
Keyword
Milling, Comminution, Powder flow, Amorphisation, Raman spectroscopy, Atomic force microscopy, Plastic stiffness, Elastic stiffness
National Category
Pharmaceutical Sciences
Research subject
Pharmaceutical Science
Identifiers
urn:nbn:se:uu:diva-317801 (URN)978-91-554-9860-3 (ISBN)
Public defence
2017-05-12, B22, BMC, Husargatan 3, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2017-04-21 Created: 2017-03-19 Last updated: 2017-05-10

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Pazesh, SamanehAlderborn, Göran

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